D-homosteroid lactones

ABSTRACT

A novel class of D-homosteroid lactones is disclosed. The compounds are useful in controlling the mineral balance of the body and thus in the treatment of oedemas.

United States Patent [191 Alig et al.

[ Nov. 18, 1975 D-HOMOSTEROID LACTONES [75] Inventors: Leo Alig, Liestal; Andor Fiirst,

Basel; Peter Keller, Therwil; Marcel Miiller, Frenkendorf, all of Switzerland; Ulrich Kerb; Rudolf Wiechert, both of Berlin, Germany [73] Assignee: Hoffmann-La Roche lnc., Nutley,

[22] Filed: Sept. 23, 1974 [21] Appl. No.: 508,127

[30] Foreign Application Priority Data Sept. 26, 1973 Switzerland 13763/73 [52] US. Cl. 260/343.6; 195/51 E; 260/340.9; 260/488 B; 260/5l4.5; 260/586 E; 260/611 F; 424/279 Primary Examinew-Lorraine A. Weinberger Assistant Examiner.lane S. Myers 7 Attorney, Agent, or Firm-Samuel L. Welt; Jon S. Saxe; George M. Gould [57] ABSTRACT A novel classof D-homosteroid lactones is disclosed. The compounds are useful in controlling the mineral balance of the body and thus in the treatment of oedemas.

16 Claims, No Drawings D-HOMOSTEROID LACTONES DESCRIPTION OF THE INVENTION The D-homosteroids provided by the present inven- 5 tion have the following general formula wherein the broken lines in the 1,2-, 6,7-' and 16, 17-

positions denote optional bonds, R represents a hydrogen atom or a methyl group when a single bond is I present in the 1,2-position or a methyl group when a double bond is present in the 1,2-position and R represents a hydrogen atom or a mercapto, acylthio or alkylthio group when a single bond is present in the 6,7-position or a hydrogen atom when a double bond is present in the 6,7-position.

As used in this description and in the claims ap-- pended hereto, the term acyl denotes the residue of a saturated or unsaturated aliphatic carboxylic acid, a

cycloaliphatic, an araliphatic or an aromatic carboxylic acid preferably containing up to 15 carbon atoms. Examples of such acids are formic acid, acetic acid, pivalic acid, propionic acid, butyric acid, caproic acid, oenanthic acid, undecylenic acid, oleic acid, cyclohexylpropionic acid, cyclopentylpropionic acid, phenylacetic acid and benzoic acid. The preferred acyl groups.

are acyl groups containing from 1 m7 carbon atoms.

The term alkyl includes aliphatic, cycloaliphatic and class of D-homosteroids of formula I comprises those in which a double bond is present in the 16,17-position; for example, 7a-acetylthio-3-oxo-D-homo-2l,24 dinor-l7aoz-chola-4,16-diene-23,17a-lactone.

Examples of D-homosteroids of formula I in which R represents a hydrogen atom are. 3-oxo-19,21,24-trinor-D-,.

homo-17a0z-chol-4-ene-23 1 7a-lactone, 3-oxo- 19,21 ,24-trinor-D-homo-17a0z-cho1a-4,6-diene- 23,17a-lactone, 3-oxo-l9,21,24-trinor-D-homo-l7aachola-4,6,16-triene-23, l7a-lactone, trinor-D-homo-l 7aa-chola-l ,4,6-triene-23, l 7a-lactone and 7a-acetylthio-3-oxo-l9,21 ,24-trinor-D-homol7aa-chola-4,16-diene-23 ,17a-lactone.

According to the process provided by the present invention, the D-homosteroids of formula I hereinbefore are manufactured by a. oxidising the 3-hydroxy-A grouping in a D-homos-' teroid of the general formula 3-oxo-19,21,24-v

wherein R has the significance given earlier,

to the 3-keto-A or 3-ke to- N' grouping or, insofar as R represents a methyl group, also to. the ia-keto-A grouping, or

b. dehydrogenating a D-homosteroid of the general formula 1 III) wherein R has the significance given earlier, in the 1,2- and/or 6,7-position (in the 1,2-position only in the case when R represents a methyl group), or

c. isomerising the 5,10-double bond in a D-homosteroid of the general formula into the 4,5'position, or

d. reacting a, D-homosteroid of the general formula The oxidation of a D-homosteroid of formula II in ac-' cordance with embodiment a) of the process can be carried out according to the Oppenauer procedure (e.g. by means of aluminium isopropylate), or using an oxidising agent such as chromium trioxide (e.g., Jones reagent), or according to the Pfitzner-Moffatt procedure using dimethyl sulphoxide/dicyclohexylcarbodiimide (the initially obtained A -3-ketone requiring subsequent isomerisation to the A -3-ketone), or using pyridine/sulphur trioxide. When an aforementioned oxidising agent such as Br /LiBr/Li CO in dimethylformamide is used or when the oxidation iscarried out according to the Oppenauer procedure in the presence of benzoquinone there is obtained a D-homosteroid containing a 3-keto-A grouping. 2,3-Dichloro-5,6- dicyano-benzoquinone is, for example, suitable for the oxidation to a D-homosteroid containing a 3-keto-A grouping.

The 1,2-dehydrogenation of a D-homosteroid of formula III in accordance with embodiment b) of the process can be carried'out in a manner known per se; for example, in a microbiological manner or using a dehydrogenating agent such as selenium dioxide, 2,3- dichloro-5,6-dicyano-benzoquinone, chloranil, thallium triacetate or lead tetraacetate. Suitable microorganisms for the 1,2-dehydrogenation are, for example, Schizomycetes, especially those of the genera Arthrobacter (e.g. A. simplex ATCC 6946), Bacillus (e.g. B. lentus ATCC; 13805 and B. sphaericus ATCC 7055), Pseudomonas (e.g. P. aeruginosa [F0 3505), Flavobacterium (e.g. F. flavescens IFO 3058), Lactobacillus (e.g.-L. brevis [F0 3345) and Nocardia (e.g. N. opaca ATCC 4276). l

The introduction of a A -double bond into a 6,7- saturated D-homosteroid of formula 111 can be carried out, for example, using a substituted-benzoquinone such as chloranil [see J. Am. Chem. Soc. 82, 4293 (1960); 81, 5951 (1959)] or using 2,3-dichloro-5,6- dicyano-benzoquinone or using manganese dioxide [see J. Am. Chem. Soc. 75, 5932 (1953)].

A 1,4,6-trisdehydro D-homosteroid can be obtained directly from a 6,7-saturated D-homosteroid of formula III in which R represents a methyl group using 2,3- dichloro-S,6-dicyano-benzoquinone or chloranil.

The isomerisation of a D-homosteroid of formula IV in accordance with embodiment c) of the process can be carried out in a manner known per se; for example, by treatment with acidic or basic agents, suitably by warming with mineral acids such as 6-N hydrochloric acid or with an alkali such as aqueous-alcoholic sodium hydroxide or potassium hydroxide at room temperature.

The introduction of a substituent denoted by R into a D-homosteroid of formula V in accordance with embodiment d) can be carried out in a manner known per se by reaction with hydrogen sulphide, a mercaptan or a thiocarboxylic acid. The reaction can be carried out in an inert solvent such as an ether (e.g. dioxane or tetrahydrofuran), an alcohol (e.g. methanol or ethanol) or a chlorinated hydrocarbon (e.g. chloroform). The reagent (e.g. the thiocarboxylic acid) is expediently used in excess amounts and can thereby serve as the solvent.

The D-homosteroid starting materials can be prepared as follows:

A Grignard compound is prepared from l7aa-ethynyl-3B, 1 7a-dihydroxy-D-homo-androst-5-ene in a manner known per se and is converted into the propiolic acid derivative with carbon dioxide. The sodium salt of the thus-obtained propiolic acid derivative is hydrogenated using palladium-on-carbon in aqueous ethanol until one mol equivalent of hydrogen has been taken up. The resulting acrylic acid derivative lactonises spontaneously and is hydrogenated with the uptake of a second mol equivalent of hydrogen to give a D-homosteroid of formula II in which a single bond is present in the 16,17-position and in which R represents a methyl group. D-homosteroid starting materials of formula II in which a single bond is present in the 16,17-position and in which R represents a hydrogen atom can be prepared as follows:

D-homooestrone methyl ether is reduced according to the Birch procedure to give D-homo-2,5( l0)-oestradine-3,17aB-diol-3-methyl ether, this is oxidised (e.g. according to the Pfitzner-Moffatt procedure) to the l7a-ketone and the ketone is reacted with an ethynyl- Grignard compound. Weak acidic hydrolysis thereof (e.g. using oxalic acid) yields D-homo-17aa-ethynyl- 17a-hydroxy-5( lO)-oestren-3-one from which, by a Grignard reaction using carbon dioxide and hydrogenation as described earlier in connection with the 10- methyl compound, there is obtained 3-(D-homo- 3B,17aB-dihydroxy-5( 1O )-oestren-1 7aa-yl )-propionic acid lactone. Oxidation (e.g. according to the Pfitzner- Moffatt procedure) yields 3-(D-homo-l7aB-hydroxy- 3-oxo-5( 10)-oestren-17aoz-yl)-propionic acid lactone, i.e. a D-homosteroid of formula IV in which a single bond is present in the 16,17-position.

D-homosteroid starting materials which contain a double bond in the 16,17-position are expediently prepared by introducing a C unit at the l7a-position of a D-homo-S, l 6-androstadien-3/3-oll 7a-one (for the preparation of starting materials in which R represents a methyl group) in a manner known per se; for example, by reaction with a Grignard reagent such as or, preferably, with the corresponding lithium compound, converting the protected-aldehyde function into an acid function and lactonising the resulting product by acidification. In an analogous manner, D-homosteroid starting materials in which a double bond is present in the 16,17-position and in which R represents a hydrogen atom can be prepared by introducing a 16,17-double bond into D-homooestrone methyl ether by bromination and dehydrobromination and then, in a manner analogous to that described earlier, carrying out a Birch reduction on the aromatic ring, oxidising a l7a-hydroxy group, introducing a propionic acid sidechain by means of a Grignard reaction, or condensation with propiolic acid in the presence of potassium hydroxide, lactonising the propionic acid side-chain and hydrolysing the 3-ether group.

The D-homosteroids of formulae II-V hereinbefore are novel and it will be appreciated that they also form part of the present invention.

The D-homosteroids of formula I hereinbefore possess pharmacological activity, their activity on the mineral reserves of the body being of particular interest. They may be used, inter alia, for flushing oedemas which are caused, for example, by heart insufficiencies.

The D-homosteroids of formula I hereinbefore may be used as medicaments; for example, in the form of pharmaceutical preparations which contain them in association with a compatible pharmaceutical carrier. This carrier can be an inert organic or inorganic carrier material suitable for enteral, percutaneous or parenteral administration such as, for example, water, gelatine, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, polyalkyleneglycols, petroleum jelly and the like. The pharmaceutical preparations can be made up in a solid form (e.g. as tablets, dragees, suppositories or capsules), in a semi-solid form (e.g. as salves) or in a liquid form (e.g. as solution, suspensions or emulsions). The pharmaceutical preparations may be sterilised and/or may contain adjuvants such as preservatives, stabilisers, wetting agents, emulsifiers, salts for varying the osmotic pressure or buffers. The pharmaceutical preparations may also contain therapeutically valuable substances other than the D-homosteroids provided by the present invention.

The pharmaceutical preparations can be prepared in a manner known per se by mixing a D-homosteroid of formula I with non-toxic, solid and/or liquid carrier materials which are customary in pharmaceutical preparations and which are suitable for therapeutic administration (e.g. those carrier materials mentioned hereinbefore) and, if desired, transforming the mixture into the desired pharmaceutical dosage form. The pharmaceutical preparations can be administered in a'dosage range similar to that required for structurally related steroids having a five-membered D-ring.

The following Examples illustrate the process provided by the present invention:

EXAMPLE 1 80 ml of solvent were distilled off while stirring and gassing with argon from a mixture of 12.50 g of 3B- hydroxy-D-homo-2 l ,24-dinorl 7aa-chol-5-ene- 23,17a-lactone, 160 ml of cyclohexanone and 400 ml of toluene. 15.0 g of aluminium tertbutylate were then added and the mixture was heated for 2 hours under reflux and under a water-separator. For the working-up, the mixture was evaporated to a volume of ca 200 ml, poured on to ice-water/dilute hydrochloric acid and extracted with methylene chloride. The methylene chloride extract was washed with water, dried over sodium sulphate and evaporated in vacuo. The residue was freed from solvent and low molecular weight condensation products at 140C in a high vacuum and then chromatographed on silica gel. By elution with methylene chloride/acetone (95:5), there were isolated 10.3 g of pure 3-oxo-D-homo-2 l ,24-dinor- 1 7aa-chol-4-ene- 23,17a-lactone of melting point 220221C (from acetone/isopropyl ether); e 16600; [41],, 25 +72.

The starting material was prepared as follows:

3B-Acetoxy-1 7a-ethynyl- 1 7-hydroxy-D-homoandrost-S-ene was converted using, butyl-lithium into the lithium salt which was reacted with carbon dioxide to give 3B,l7aB-dihydroxy-D-homopregn- 5-en-20-yne-2l-carboxylic acid of melting point 194196C; [01],, l23. This acid was catalytically hydrogenated in alkaline solution and, after acidification, yielded 3B-hydroxy-D-homo-21,24- dinor-17aa-chola-5 ,20-diene-23,1 7a-lactone of melting point 205-207C; [01],, 43. This lactone was catalytically hydrogenated using palladium-on-carbon in ethanol to give 3 B-hydroxy-D- homo-21 ,24-dinor-17aa-chol-5-ene-23,l7a-lactone of melting point 240243C [01],, 99 (0 0:1 in dioxane).

EXAMPLE 2 A solution of 4.0 g of 3-oxo-D-homo-21,24-dinorl7aa-chol-4-ene-23,17a-lactone in 200 ml of dioxane containing 6.5% HCl was treated over a period of 3 minutes with a solution of 3.1 g of 2,3-dichloro-5,6 dicyano-benzoquinone in 50 m1 of dioxane containing 6.5% HCl. The mixture was then stirred for 7 minutes 4,6-diene-23,l7a-lactone of melting point 242-244C;

6 27200; =+25 (c 0.1 in dioxane). By elution with methylene chloride/acetone (9:1), there was finally obtained 3-oxo-D-homo-21 ,24-dinor-1 7aachola-1,4,6-triene-23,l7a-lactone of melting point 179-180C; e 11600, e 9300, e 12500; [04 +15 (C 0.1 in dioxane).

EXAMPLE 3 A solution of 0.50 g of 3-oxo-l9-nor-D-homo-21,24- dinor-l7aa-chol-5(10)-ene-23,17a-lactone in 50 m1 of dioxane containing 2% HCl was held at room temperature for 2 hours. For the working-up, the mixture was poured on to ice-water and extracted with methylene' chloride. The methylene chloride extract was washed neutral with water, dried over sodium sulphate and evaporated in vacuo. After recrystallisation of the residuefrom acetone/hexane,, there was obtained pure 3- oxo-19-nor-D-homo-21 ,24-dinor-l7aa-cho1-4-ene- 23,17a-lactone; 6 16800.

The starting material was prepared as follows:

D-homooestrone' methyl ether was reduced according to the Birch procedure and subsequently oxidised according to the Pfitzner-Moffatt procedure to give 3- methoxy-D-homooestra-2 ,5 10 )-dien- 1 7a-one. This was ethynylated using potassium acetylide to give 1 7aa-ethynyl-17-hydroxy-3-methoxy-D-homooestra- 2,5(10)-diene which was reacted, via the corresponding lithium compound, with carbon dioxide to give 1 7aB-hydroxy-3-methoxy- 1 9-nor-D-homo-pregna- 2,5( l0)-dien-20a-yne-21carboxylic acid. Partial catalytic hydrogenation of this carboxylic acid in alkaline solution and subsequent treatment with oxalic acid in dioxane yielded 3-oxo-19-nor-D-homo-21,24-dinorl7a0z-chola-5( l0),20-diene-23,17a-lactone which was converted by selective catalytic hydrogenation into 3- oxo-l9-nor-D-homo-21,24-dinor-l7aa-chol- 5(10)-ene-23,17a-lactone.

EXAMPLE 4 A solution of 1.0 g of 3-oxo-D-homo-2l,24-dinorl7aa-chola-4,6-diene-23,17a-lactone in 6 ml of thioacetic acid was held at room temperature for 3 hours. The mixture was poured on to ice-water and extracted with ether. The ether extract was washed with dilute sodium hydroxide and water, dried over sodium sulphate and evaporated in vacuo. The residue was chrmatographed over silica gel. Elution with ether/hexane lzl yielded pure 7a-acetylthio-3-oxo-D-homo-2l.24- dinor-l7aa-chol-4-ene-23,l7a-lactone of melting point l93l95C (from methanol); 6 1900; [01],, 26 (c 0.1 in dioxane).

EXAMPLE 1.4 g of 3,8-hydroxy-D-homo-21,24-dinor-l 7aa-chol- 5-ene-23 ,l7a-lactone, 1.8 g of lithium bromide and 1.8

- g of lithium carbonate were warmed to 80C in 30 ml of dimethylformamide and treated over a period of 45.

minutes with a solution of 1.32 g of bromine in 9.2 ml of dioxane. The mixture was subsequently warmed to 80C for a further 2 hours. The mixture was then poured on to water and acidified with acetic acid. The precipitate was filtered off and recrystallised twice from acetone/hexane. There was obtained pure 3-oxo- D-homo-2 l ,24-dinorl 7aa-chola-4,6-diene-23, 17alactone of melting point 242-244C. 7

EXAMPLE 6 1.5 g of 3-oxo-D-homo-21,24-dinor-1 7aa-chola-4,6-

EXAMPLE 7 5.0 g of 3B-hydroxy-D-homo-21,24-dinor-l7aachola-5,l6-diene-23,l7a-lactone were dissolved in ml of dimethyl sulphoxide and 25 ml of benzene. 1.2 ml of pyridine and 0.6 ml of trifluoroacetic acid were added while stirring and gassingwith argon. 7.6 g of N,N-dicyclohexylcarbodiimide were then added and the mixture was stirred overnight at room temperature. A mixture of 3.4 g of oxalic acid, 31 ml of methanol and 350 ml of ether was then added to the slightly yellowish suspension and the resulting mixture was stirred for a further 1 hour. For the working-up, the mixture I was treated with 400 ml of water, stirred for 15 minutes and then filtered. The filtrate was washed successively with sodium bicarbonate solution and water, dried.over sodium sulphate and evaporated in vacuo. The crude product was dissolved in 150 ml of acetic acid and 15 ml of 2-N hydrochloric acid held at room temperature for 1 hour. The solution was then poured on to icewater, extracted with methylene chloride and the meth-v ylene chloride extracts washed with sodium carbonate solution and water. After drying over sodium sulphate, the solvent was evaporated in vacuo and the residue recrystallised from acetone/hexane. There was obtained pure 3-oxo-D-homo-2l ,24-dinorl 7aa-chola-4. 16- diene-23, 17a-lactone of melting point 2l82l9C; e 16650.

The starting material was prepared as follows:

3,8-Acetoxy-D-homo-androst-5-en-l 7a-one was brominated with CuBr and, by subsequent treatment with calcium carbonate in dimethylacetamide and acetylation with acetic anhydride/pyridine, converted into 33- acetoxy-D-homoandrosta-S, l 6-dien-l 7a-one. This compound was converted, by treatment with 3B-ethylenedioxy-n-propyl-magnesium bromide and subsequent acetylation, into 3B-acetoxy-l7aa-(3,3'- ethylenedioxa-propyl l 7a-hydroxy-D-homoandrost- 5-ene. Acid saponification of this ethylene ketal, oxidation'according to theJones procedure, saponification of the BB-acetoxy group with potassium carbonate and subsequent treatment with acid yielded 3B-hydroxy-D- homo-21 ,24-dinor-l7aa-chola-5,l6-diene-23,l7a-lactone.

EXAMPLE 8 In a manner analogous to that described in Example 5,- from 3B-hydrox y-D-homo-2 l ,24-dinor- 1 7aa-chola- 5,l6-diene-2'3.l7a-lactone there was obtained 3-oxo- D-homo-2 l ,24-dinorl 7aa-chola-4,6, l 6-triene- 23,27a-lactone of melting point 2l42l4.5C.

.' EXAMPLE 9 In a manner analogous to that described in Example 4, from 3-oxo-D-homo-2 l ,24-dinorl 7aa-chola- 4,6,16-triene 23,17a-lactone there was obtained acetylthio-3-oxo-2l ,24-dinorl 7aa-chola-4, l 6-diene- 23,17a-lactone, m. p. l43-l45 (from acetone-isopropyl ether).

We claim:

l. A D-homosteroid of the general formula wherein the broken lines in the l,2-,6,7- and 16,17- positions denote optional bonds, R is a hydrogen atom or methyl when a single bond is present in the 1,2- position or methyl when a double bond is present in the 1,2-position and R is hydrogen, mercapto, C -hydrocarbon acylthio or C alkylthio when a single bond is present in the 6,7-position or hydrogen when a double bond is present in the 6,7-position.

2. A D-homosteroid of claim 1, wherein R is methyl.

3. A D-homosteroid of claim 2, wherein a single bond is presentin the 1,2-position and a double bond is present in the 16,17-position.

4. The compound of claim 3 which is 3-oxo-D-h0mo- 2l ,24-dinorl 7aa-chola-4, l 6-diene-23, l 7a-lactone.

5. The compound of claim 3 which is 7a-acetylthio- 3-oxo-2 l ,24-dinor-1 7aqz-chola-4, l 6-diene-23, l 7a-lactone. i

6. The compound of claim 3 which is 3-oxo-D-homo- 21 ,24-dinorl 7aa-chola-4,6, l 6-triene-23, l 7a-lactone.

7. A compound'of claim 2 wherein a single bond is present'in the 1',2-,6,7-, and 16,17-p0sitions.

8. The compound of claim 7 which is 3-oxo-D-homo- 21 ,24-dinorl 7aoz-chol-4-ene-23,l 7a-lactone.

9. The compound of claim 7 which is 3-oxo-l9-nor- D-homo-2l ,24-dinorl 7aa-chol-4-ene-23, l 7a-lactone.

10. The compound of claim 7 which is 7oz-acetylthio- 3-oxo-D-homo-2 l ,24-dinorl 7aoz-chol-4-ene-23,l 7alactone.

11. A compound of claim 2 wherein a single bond is present in the 1,2- and l6,l7-position and a double bond is present in the 6,7-position.

12. The compound of claim 11 which is 3-oxo-D- homo-21 ,24-dinorl 7aa-chola-4,6-diene-23, l 7a-lactone.

13. A compound of claim 2 wherein a single bond is present in the 16, l 7-position and a double bond is present in the 1,2- and 6,7-positions.

14. The compound of claim 13 which is 3-oxo-D- homo-21 ,24-dinorl 7aa-chola-4, l 6-diene-23 l 7a-lactone.

15. A compound of the formula wherein the broken line in l6,l7-position denotes an optional bond. 

1. A D-HOMOSTEROID OF THE GENERAL FORMULA
 2. A D-homosteroid of claim 1, wherein R10 is methyl.
 3. A D-homosteroid of claim 2, wherein a single bond is present in the 1,2-position and a double bond is present in the 16,17-position.
 4. The compound of claim 3 which is 3-oxo-D-homo-21,24-dinor-17a Alpha -chola-4,16-diene-23,17a-lactone.
 5. The compound of claim 3 which is 7 Alpha -acetylthio-3-oxo-21,24-dinor-17a Alpha -chola-4,16-diene-23,17a-lactone.
 6. The compound of claim 3 which is 3-oxo-D-homo-21,24-dinor-17a Alpha -chola-4,6,16-triene-23,17a-lactone.
 7. A compound of claim 2 wherein a single bond is present in the 1,2-,6,7-, and 16,17-positions.
 8. The compound of claim 7 which is 3-oxo-D-homo-21,24-dinor-17a Alpha -chol-4-ene-23,17a-lactone.
 9. The compound of claim 7 which is 3-oxo-19-nor-D-homo-21,24-dinor-17a Alpha -chol-4-ene-23,17a-lactone.
 10. The compound of claim 7 which is 7 Alpha -acetylthio-3-oxo-D-homo-21,24-dinor-17a Alpha -chol-4-ene-23,17a-lactone.
 11. A compound of claim 2 wherein a single bond is present in the 1,2- and 16,17-position and a double bond is present in the 6,7-position.
 12. The compound of claim 11 which is 3-oxo-D-homo-21,24-dinor-17a Alpha -chola-4,6-diene-23,17a-lactone.
 13. A compound of claim 2 wherein a single bond is present in the 16,17-position and a double bond is present in the 1,2- and 6,7-positions.
 14. The compound of claim 13 which is 3-oxo-D-homo-21,24-dinor-17a Alpha -chola-4,16-diene-23,17a-lactone.
 15. A COMPOUND OF THE FORMULA
 16. A COMPOUND OF THE FORMULA 